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2009). Exposure to hydrogen peroxide resulted in a rapid increase in MitoSOX Red fluorescence and the magnitude of this increase did not differ between mtDNA mutator and Control http://www.selleck.cn/products/lee011.html fibres (Fig. 4A). We also measured protein expression of SOD2, located in the mitochondrial matrix, and SOD1, located in the cytosol and mitochondrial intermembrane space, and their expression levels were similar in mtDNA mutator and Control muscles (Fig. 4B). We used Western blotting to measure the expression of several proteins important for the control of mitochondrial biogenesis. PGC-1��, a key regulator of oxidative metabolism and trigger of mitochondrial biogenesis (Handschin & Spiegelman, 2006; Arany, 2008), was ?45% lower in young mtDNA mutator than in Control muscles (Fig. 5A). PPAR-��, a transcription factor that promotes fatty acid transport and mitochondrial fatty acid ��-oxidation (Berger & Moller, 2002), showed ?30% lower levels in mtDNA mutator than in Control muscles (Fig. 5B). Finally, AMPK, http://www.selleckchem.com/products/i-bet-762.html a key sensor of cellular energy status (Hardie, 2011), was ?25% lower in mtDNA mutator muscles than in Controls (Fig. 5C). Muscle contractile properties were measured in EDL muscles isolated from end-stage (11 months) mtDNA mutator mice and age-matched Controls. At this age, mtDNA mutator EDL muscles showed decreased weight (7.7 �� 0.3 vs. 11.2 �� 0.6 mg) and cross-sectional area (0.79 �� 0.06 vs. 1.01 �� 0.04 mm2) compared with Controls (P http://www.selleckchem.com/products/epacadostat-incb024360.html mtDNA mutator mice than in Control fibres (Fig. 6B and C; P